Bacteria utilize diverse biochemical pathways for the degradation of the pyrimidine ring. The function of the pathways studied to date has been the release of nitrogen for assimilation. The most widespread of these pathways is the reductive pyrimidine catabolic pathway, which converts uracil into ammonia, carbon dioxide and β-alanine. Here we report the characterization of a β-alanine:pyruvate aminotransferase (PydD2), and a NAD⁺-dependent malonic semialdehyde dehydrogenase (MSDH), from a reductive pyrimidine catabolism gene cluster in Bacillus megaterium. Together, these enzymes convert β-alanine into acetyl-CoA, a key intermediate in carbon and energy metabolism. We demonstrate the growth of B. megaterium in defined medium with uracil as its sole carbon and energy source. Homologs of PydD2 and MSDH are found in association with reductive pyrimidine pathway genes in many Gram positive bacteria in the order Bacillales. Our study provides a basis for further investigations of the utilization of pyrimidines as a carbon and energy source by bacteria.

Importance Pyrimidine has wide occurrence in natural environments, where bacteria use it as nitrogen and carbon source for growth. Detailed biochemical pathways have been investigated with focus mainly on nitrogen assimilation in the past decades. Here we report the discovery and characterization of two important enzymes, PydD2 and MSDH, which constitute an extension for the reductive pyrimidine catabolic pathway. These two enzymes, prevalent in Bacillales based on our bioinformatics studies, allow stepwise conversion of β-alanine, a previous "end product" of the reductive pyrimidine degradation pathway to acetyl-CoA, as carbon and energy source.

细菌利用多种生化途径降解嘧啶环。迄今为止研究的途径的功能是释放氮以进行同化。这些途径中最广泛的是还原性嘧啶分解代谢途径，其将尿嘧啶转化为氨，二氧化碳和β-丙氨酸。在这里，我们报道了来自巨大芽孢杆菌中还原性嘧啶分解代谢基因簇的β-丙氨酸：丙酮酸转氨酶（PydD2）和NAD ⁺依赖性丙二醛半醛脱氢酶（MSDH）的表征。这些酶共同将β-丙氨酸转化为乙酰辅酶A，这是碳和能量代谢的关键中间体。我们证明了巨大芽孢杆菌的生长在以尿嘧啶为唯一碳源和能源的特定介质中。在许多革兰氏阳性细菌中，PydD2和MSDH的同系物与还原嘧啶途径基因相关，并以芽孢杆菌顺序排列。我们的研究为进一步研究细菌利用嘧啶作为碳和能源提供了基础。

重要性嘧啶在自然环境中广泛存在，细菌将其用作生长的氮和碳源。在过去的几十年中，已经详细研究了详细的生化途径，重点是氮的吸收。在这里我们报告发现和表征两个重要的酶，PydD2和MSDH，它们构成了还原嘧啶分解代谢途径的延伸。根据我们的生物信息学研究，这两种酶普遍存在于芽孢杆菌中，它们可以逐步将β-丙氨酸（一种还原性嘧啶降解途径的先前“最终产物”）转化为乙酰辅酶A作为碳和能源。